ArchSchema: a tool for interactive graphing of related Pfam domain architectures

Tamuri, Asif U.; Laskowski, Roman A.

doi:10.1093/bioinformatics/btq119

Cited by 21 publications

(17 citation statements)

References 12 publications

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“…by changing the domain partners [24] or through the duplication and diversification of domains [25]. To explore how the addition of domains can affect a given domain's function, a different sub-clustering of the superfamily was made based on the unique multi-domain architecture identified using ArchSchema [26]. Proteins that contain the superfamily domains in the same order are clustered together.…”

Section: Resultsmentioning

confidence: 99%

“…Any unassigned sequence regions large enough to constitute a domain are checked against Pfam and if a non-overlapping Pfam domain is found then it is included in the MDA. Sequences with the same multi-domain architectures are clustered using ArchSchema [26]. The sequences of each cluster are then aligned using MAFFT [43], and the alignment used to perform the phylogenetic analysis.…”

Section: Methodsmentioning

confidence: 99%

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Exploring the Evolution of Novel Enzyme Functions within Structurally Defined Protein Superfamilies

et al. 2012

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In order to understand the evolution of enzyme reactions and to gain an overview of biological catalysis we have combined sequence and structural data to generate phylogenetic trees in an analysis of 276 structurally defined enzyme superfamilies, and used these to study how enzyme functions have evolved. We describe in detail the analysis of two superfamilies to illustrate different paradigms of enzyme evolution. Gathering together data from all the superfamilies supports and develops the observation that they have all evolved to act on a diverse set of substrates, whilst the evolution of new chemistry is much less common. Despite that, by bringing together so much data, we can provide a comprehensive overview of the most common and rare types of changes in function. Our analysis demonstrates on a larger scale than previously studied, that modifications in overall chemistry still occur, with all possible changes at the primary level of the Enzyme Commission (E.C.) classification observed to a greater or lesser extent. The phylogenetic trees map out the evolutionary route taken within a superfamily, as well as all the possible changes within a superfamily. This has been used to generate a matrix of observed exchanges from one enzyme function to another, revealing the scale and nature of enzyme evolution and that some types of exchanges between and within E.C. classes are more prevalent than others. Surprisingly a large proportion (71%) of all known enzyme functions are performed by this relatively small set of 276 superfamilies. This reinforces the hypothesis that relatively few ancient enzymatic domain superfamilies were progenitors for most of the chemistry required for life.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Exploring the Evolution of Novel Enzyme Functions within Structurally Defined Protein Superfamilies

et al. 2012

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“…However, structural and biochemical analysis showed these enzymes to be very different from each other: 2A9S contains the conserved residues responsible for NMN deamidase activity [7], whereas 3KBQ has been recently described as a new class of pyrophosphatase (eggNOG code: COG1058) [11]. When the structure of A. tumefaciens CinA (2A9S) was studied in detail using ArchSchema [12], a tool for interactive graphing of related Pfam domain architectures, three well-defined groups could be identified attending to domain composition (Figure 2). The first covers enzymes with the same architecture than 2A9S, showing only a CinA domain (Pfam code: PF02464), whereas the second shows enzymes containing one CinA domain bound to a N-terminal sequence tail of unknown function, generally associated with strains of Helicobacter pylori (Pfam code: PB027750) and a few in α- and γ-proteobacteria.…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Phylogeny and Molecular Classification of Nicotinamide Mononucleotide Deamidases

et al. 2013

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Nicotinamide mononucleotide (NMN) deamidase is one of the key enzymes of the bacterial pyridine nucleotide cycle (PNC). It catalyzes the conversion of NMN to nicotinic acid mononucleotide, which is later converted to NAD+ by entering the Preiss-Handler pathway. However, very few biochemical data are available regarding this enzyme. This paper represents the first complete molecular characterization of a novel NMN deamidase from the halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiPncC). The enzyme was active over a broad pH range, with an optimum at pH 7.4, whilst maintaining 90 % activity at pH 10.0. Surprisingly, the enzyme was quite stable at such basic pH, maintaining 61 % activity after 21 days. As regard temperature, it had an optimum at 65 °C but its stability was better below 50 °C. OiPncC was a Michaelian enzyme towards its only substrate NMN, with a K m value of 0.18 mM and a kcat/K m of 2.1 mM-1 s-1. To further our understanding of these enzymes, a complete phylogenetic and structural analysis was carried out taking into account the two Pfam domains usually associated with them (MocF and CinA). This analysis sheds light on the evolution of NMN deamidases, and enables the classification of NMN deamidases into 12 different subgroups, pointing to a novel domain architecture never before described. Using a Logo representation, conserved blocks were determined, providing new insights on the crucial residues involved in the binding and catalysis of both CinA and MocF domains. The analysis of these conserved blocks within new protein sequences could permit the more efficient data curation of incoming NMN deamidases.

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“…the same MDA. Grouping of MDAs is carried out by ArchSchema (19), which also visualizes the relationships between MDAs as a directed graph. For each superfamily, entire protein sequences which share the same MDA are aligned using MAFFT (20).…”

Section: The Funtree Pipelinementioning

confidence: 99%

FunTree: a resource for exploring the functional evolution of structurally defined enzyme superfamilies

Furnham

Sillitoe

Holliday

et al. 2011

Nucleic Acids Research

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FunTree is a new resource that brings together sequence, structure, phylogenetic, chemical and mechanistic information for structurally defined enzyme superfamilies. Gathering together this range of data into a single resource allows the investigation of how novel enzyme functions have evolved within a structurally defined superfamily as well as providing a means to analyse trends across many superfamilies. This is done not only within the context of an enzyme's sequence and structure but also the relationships of their reactions. Developed in tandem with the CATH database, it currently comprises 276 superfamilies covering ∼1800 (70%) of sequence assigned enzyme reactions. Central to the resource are phylogenetic trees generated from structurally informed multiple sequence alignments using both domain structural alignments supplemented with domain sequences and whole sequence alignments based on commonality of multi-domain architectures. These trees are decorated with functional annotations such as metabolite similarity as well as annotations from manually curated resources such the catalytic site atlas and MACiE for enzyme mechanisms. The resource is freely available through a web interface: www.ebi.ac.uk/thorton-srv/databases/FunTree.

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ArchSchema: a tool for interactive graphing of related Pfam domain architectures

Cited by 21 publications

References 12 publications

Exploring the Evolution of Novel Enzyme Functions within Structurally Defined Protein Superfamilies

Exploring the Evolution of Novel Enzyme Functions within Structurally Defined Protein Superfamilies

New Insights into the Phylogeny and Molecular Classification of Nicotinamide Mononucleotide Deamidases

FunTree: a resource for exploring the functional evolution of structurally defined enzyme superfamilies

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